| First Author | Cijsouw T | Year | 2014 |
| Journal | J Cell Biol | Volume | 204 |
| Issue | 5 | Pages | 759-75 |
| PubMed ID | 24590174 | Mgi Jnum | J:217249 |
| Mgi Id | MGI:5613442 | Doi | 10.1083/jcb.201308026 |
| Citation | Cijsouw T, et al. (2014) Munc18-1 redistributes in nerve terminals in an activity- and PKC-dependent manner. J Cell Biol 204(5):759-75 |
| abstractText | Munc18-1 is a soluble protein essential for synaptic transmission. To investigate the dynamics of endogenous Munc18-1 in neurons, we created a mouse model expressing fluorescently tagged Munc18-1 from the endogenous munc18-1 locus. We show using fluorescence recovery after photobleaching in hippocampal neurons that the majority of Munc18-1 trafficked through axons and targeted to synapses via lateral diffusion together with syntaxin-1. Munc18-1 was strongly expressed at presynaptic terminals, with individual synapses showing a large variation in expression. Axon-synapse exchange rates of Munc18-1 were high: during stimulation, Munc18-1 rapidly dispersed from synapses and reclustered within minutes. Munc18-1 reclustering was independent of syntaxin-1, but required calcium influx and protein kinase C (PKC) activity. Importantly, a PKC-insensitive Munc18-1 mutant did not recluster. We show that synaptic Munc18-1 levels correlate with synaptic strength, and that synapses that recruit more Munc18-1 after stimulation have a larger releasable vesicle pool. Hence, PKC-dependent dynamic control of Munc18-1 levels enables individual synapses to tune their output during periods of activity. |
